Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level

Gemma Swiers, Claudia Baumann, John O’Rourke, Eleni Giannoulatou, Stephen Taylor, Anagha Joshi, Victoria Moignard, Cristina Pina, Thomas Bee, Konstantinos D. Kokkaliaris, Momoko Yoshimoto, Mervin C. Yoder, Jon Frampton, Timm Schroeder, Tariq Enver, Berthold Göttgens and Marella F. T. R. de Bruijn ()
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Gemma Swiers: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Claudia Baumann: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
John O’Rourke: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Eleni Giannoulatou: Computational Biology Research Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Stephen Taylor: Computational Biology Research Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Anagha Joshi: Cambridge Institute for Medical Research and Wellcome Trust & MRC Cambridge Stem Cell Institute
Victoria Moignard: Cambridge Institute for Medical Research and Wellcome Trust & MRC Cambridge Stem Cell Institute
Cristina Pina: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Thomas Bee: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Konstantinos D. Kokkaliaris: Research Unit Stem Cell Dynamics, Helmholtz Center Munich–German Research Center for Environmental Health
Momoko Yoshimoto: Wells Center for Pediatric Research, Indiana University School of Medicine
Mervin C. Yoder: Wells Center for Pediatric Research, Indiana University School of Medicine
Jon Frampton: Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham
Timm Schroeder: Research Unit Stem Cell Dynamics, Helmholtz Center Munich–German Research Center for Environmental Health
Tariq Enver: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
Berthold Göttgens: Cambridge Institute for Medical Research and Wellcome Trust & MRC Cambridge Stem Cell Institute
Marella F. T. R. de Bruijn: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: Abstract Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP+ HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment.

Date: 2013
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DOI: 10.1038/ncomms3924

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